Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease. The development of complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan has revolutionized the management of PNH, leading to improvements in overall survival and quality of life for patients.
Objectives: This systematic review aims to provide comprehensive evidence of the efficacy of complement inhibitors in relation to treatment duration.
Design: This is a systematic review and meta-analysis.
Data sources and methods: A thorough literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library up to 3 May 2022. We included all prospective interventional studies including single-arm trials. The primary outcomes of interest were lactate dehydrogenase (LDH) levels, hemoglobin (Hb) concentrations, transfusion avoidance, and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores.
Results: Our study included a total of 27 studies, comprising 5 randomized controlled trials and 11 single-arm trials, with a total of 912 patients with PNH. We stratified the studies according to treatment duration, based on the most frequently reported period of 26 weeks. Our analysis showed that treatment-naïve patients who received complement inhibitors had a pooled estimate of a decrease in LDH levels from baseline by -1462.0 U/L (95% CI: -1735.6 to -1188.5) for treatment ⩽26 weeks and -1696.5 U/L (95% CI: -2122.7 to -1270.2) for treatment >26 weeks. The mean Hb levels were increased by 1.4 g/dL (95% CI: 0.5-2.3) and 1.9 g/dL (95% CI: 0.7-3.1) in each group. Treatment with any complement inhibitor prevented the need for transfusion in at least 50% of patients with PNH in all treatment periods. Clinically meaningful improvements in FACIT-F were observed both before and after 26 weeks, with a pooled estimate of 6.8 (95% CI: 6.0-7.6) and 9.5 (95% CI: 7.0-12.0), respectively.
Conclusion: Our findings suggest that complement inhibitors can result in positive treatment outcomes and sustained benefits for patients with PNH.
Keywords: clinical outcomes; complement inhibitors; eculizumab; paroxysmal nocturnal hemoglobinuria; pegcetacoplan; rare disease; ravulizumab